The Silexan in the Treatment Of Posttraumatic stress disorder (STOP) trial: protocol for a 12-week randomised controlled trial of adjunctive Silexan for PTSD

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common and potentially debilitating psychiatric disorder. Current and emerging evidence-based treatments for PTSD have significant limitations. Silexan is an orally administered lavender oil preparation whose main constituents are the monoterpenoids linalool and linalyl acetate. It has a novel pharmacodynamic profile that includes inhibition of voltage-gated calcium channels and promotion of neuroplasticity. Silexan is effective in the treatment of Generalized Anxiety Disorder, subthreshold anxiety disorders and mild-to-moderate Major Depressive Disorder. It has an excellent safety and tolerability profile. Promising pilot data suggest that Silexan may be effective for PTSD. The Silexan in the Treatment Of Posttraumatic stress disorder (STOP) trial aims to investigate the effectiveness of adjunctive Silexan in PTSD. METHODS: The STOP trial is a 12-week, parallel-arm, randomised, placebo-controlled, double-blind trial. Adults living in Australia who meet diagnostic criteria for PTSD according to the Mini-International Neuropsychiatric Interview-7 and have a score of ≥ 33 on the PTSD Checklist for DSM-5 will be eligible to participate. Participants will have the option of taking part in the trial remotely via videoconferencing software. They will receive either Silexan 160 mg or an inactive placebo daily for 12 weeks in addition to their usual prescribed medications. The primary outcome measure will be the change in total symptom severity score on the Clinician-Administered PTSD Scale for DSM-5 from baseline to week 12. Secondary outcome measures will include self-report measures of anxiety symptoms, depressive symptoms, somatic symptoms, sleep quality, subjective wellbeing, quality-of-life and problematic alcohol use. Additional secondary outcome measures will include objective measures of sleep, physical activity and physiology derived from data collected by actigraphy watches. The target sample size will be 278 participants. DISCUSSION: If Silexan is found to be effective for PTSD, it is likely to be an attractive treatment option for many patients given its favourable safety and tolerability profile. Silexan is already licensed for use in 14 countries, enabling a rapid translation into clinical care. TRIAL REGISTRATION: The STOP trial is registered on the National Institutes of Health clinicaltrials.gov website (ID: NCT06412757, URL: https://clinicaltrials.gov/study/NCT06412757 , date of registration: 9 May 2024).